This is the among the first studies, to our knowledge, to use a “dismantling” study design in which the effects of a standardized, extended program of computer-assisted cognitive remediation targeted directly at neurocognitive deficits were contrasted with those of a control condition consisting of many of the elements of the treatment condition, including duration of exposure to a computer, interaction with a clinician and non-specific cognitive challenge, in order to begin to decompose the potential mechanism of actions of positive effects of computer-assisted cognitive remediation on neurocognitive function that have been reported in the literature (Bell et al., 2001
; Bellucci et al., 2002
; Medalia et al., 2001
; Seltzer et al, 1997
). The results from this study suggest that training in cognitive exercises targeted at specific neurocognitive deficits provides incremental benefit for specific aspects of neurocognition, but that exposure to a computer, interaction with a clinician and non-specific cognitive challenge produce non-specific improvement in neurocognitive function as well. More specifically, patients randomly assigned to the cognitive remediation treatment condition showed improvement in working memory that was greater than that produced by training in computer literacy alone. Non-specific effects were evident in both groups for working memory, reasoning/problem-solving, verbal and non-verbal episodic memory and processing speed. These latter findings are important as a growing number of studies have shown that neuropsychological test findings are highly stable in young-adult to middle-age patients with schizophrenia over a one to as many as 10-year longitudinal follow-up (e.g., Censits et al, 1997
; Stirling et al., 2003
; Kurtz et al., 2005
), suggesting that these non-specific effects are most likely not simply the effect of practice, task familiarity or extended pharmacologic intervention.
The remediation-linked improvements in working memory in this study are highly consistent with those reported in a previous study using a similar cognitive training protocol (Bell et al., 2001
), and suggest that neurocognitive training in skills related to holding information in mind and manipulating that information can be improved in patients with schizophrenia, even when these skills are assessed with instruments different from those used for training. The current study extends previous findings by showing that these effects can be linked to training on neurocognitive tasks per se.
Patients were administered the cognitive remediation intervention over a lengthy period of time and many patients failed to reach their goal of 100 treatment hours due to a variety of factors including greater time devoted to competitive employment or volunteer work, return to school, changes in location of home and discharge to other community care providers. Exploratory analyses investigating the relationship of hours of cognitive remediation training to z-score improvement in the working memory factor failed to show a relationship between these variables (p=.10).
The finding of a selective advantage of cognitive remediation on working memory in patients with schizophrenia, but not accompanying evidence of a commensurate advantage in the reasoning/executive-function domain in this treatment group is paradoxical as a variety of studies have shown a close link between more elementary working-memory functions and higher-level reasoning and problem-solving skills (e.g., Gold et al., 1997
). One potential hypothesis is that given the non-specific effect of treatment on working memory in the sample as a whole, some improvement in working memory may improve more complex executive-functions but only up to a threshold (perhaps to the level of average functioning), after which improved working memory does not produce accompanying improvements in executive-function. The finding that both experimental groups scored within −.5 SD of healthy control performance in the reasoning/executive-function domain after intervention supports this view.
Given that both treatment groups showed improvement in working memory function across this trial, it remains unclear exactly how much more effective cognitive remediation was for treating this domain of neurocognitive functioning. Analysis of the pattern of treatment response in individual patients indicated that large z-score improvements (≥.8 SD) were evident in 22% of patient of the cognitive remediation condition, and in no patients in the computer skills intervention, suggesting a clear advantage for cognitive remediation treatment for working memory deficits in a subgroup of patients with schizophrenia. This analysis also suggested large inter-participant variability in response to cognitive remediation.
In light of the large individual differences in response to the remediation intervention on working memory measures evident in our study, an important area of future study will be determining which patient characteristics predict these variable treatment responses. An exploratory analysis of the current data failed to show a relationship of age, age of illness onset, duration of illness or number of hospitalizations to z-score improvement in working memory for patients treated with cognitive remediation (all ps≥.36). The small sample size (n=23), however, most likely precluded detection of even moderate-size effects.
The current sample consisted of stable outpatients who typically were chronically ill (mean duration of illness=11.0 years), in early middle-age (mean age=36.7 years), and were of average estimated premorbid intelligence (mean vocabulary scaled score=10.0). It remains unclear to what degree these findings would generalize to patients earlier or later in the course of their illness, in long-term inpatient or nursing home care, or of poorer estimated premorbid intelligence. Age, outpatient status and duration of illness of our sample are similar to some positive reports of cognitive training in the literature (e.g., Bell et al., 2001
; Bellucci et al., 2002
) but not others (e.g., Medalia et al., 2001
The finding that both experimental groups showed significant improvement in a variety of neurocognitive domains suggests that the cognitive stimulation linked to repeated exposure to a computer, interaction with a clinician and the non-specific stimulation of learning and remembering information for periodic exams produces stimulation well beyond that provided in most patients’ natural environment. One potential implication of these findings is that the neurocognitive deficits and negative symptoms of the disorder place such large restrictions on patients social and occupational life, that any type of sustained, goal-directed cognitive activity in the presence of supportive clinicians, regardless of its content, has the potential to elevate neuropsychological function significantly in this patient population. Consistent with this viewpoint, a small but growing number of studies suggest that structured behavioral rehabilitation improves neurocognitive skills in patients with schizophrenia in the absence of any specific cognitive training (e.g., Spaulding et al., 1999
; Silverstein & Wilkness, 2004
). This possibility also emphasizes the significance of reports showing an advantage of cognitive remediation for a variety of outcome measures, even when cognitive remediation interventions are compared with control interventions that involve considerable non-specific stimulation such as work therapy or supported employment programs (Bell et al., 2001
; McGurk et al., 2005
The advantage of cognitive remediation for working memory function in the present study suggests however that at least some additional neurocognitive benefit may accrue from the careful titration of task difficulty of cognitive exercises to ensure appropriate cognitive challenge, the rapid repetition of demanding exercises, and the frequency of reinforcement associated with achievement of intermediate and overall task goals characteristic of this condition. The hierarchical nature of the training program, starting with training in elementary attention skills and then graduating to considerably more complex episodic and verbal memory tasks may also play a role in the advantage of this condition.
It is important to note that while the majority of randomized controlled studies of cognitive remediation in schizophrenia have not employed control conditions that were matched with the intervention for time spent on a computer, clinician interaction and “non-specific” cognitive challenge, there are several exceptions. For example, (Medalia et al., 2000
) in a study of 54 chronic inpatients with schizophrenia, compared the effects of computerized programs of problem-solving and memory training against one another, and a non-computer-trained control condition, on measures of problem-solving skill for independent living, verbal comprehension, immediate paragraph recall and verbal list learning. Results revealed that the problem-solving training produced improvements in problem-solving skills, but not comprehension or memory measures, relative to the memory-trained group that also had exposure to a computer, interaction with the same clinician and “non-specific” challenge. There was no evidence of “non-specific” effects of the control computer training on cognition in this study, however. This difference in findings from the current study may relate to differences in duration of the control interventions and the differences in patient populations studied (in- vs. outpatient).
Several limitations to the current study should be mentioned. First, sample size was small and effects of small to medium size may have been obscured secondary to limited power. Nonetheless, this observation highlights the robustness of the effects of cognitive remediation on working memory and the non-specific effects of both interventions on a variety of neurocognitive measures. Second, the relationship of cognitive-remediation-linked improvements in working memory, or non-specific improvements in working memory, reasoning/problem-solving, verbal and non-verbal episodic memory, and processing speed observed in this study, to performance-based, proxy measures of daily-life functioning and actual measures of community-function, remains unclear. We note that integration of cognitive remediation interventions similar to the type employed in the current study with work therapy or supported employment programs have produced improvements in measured work function (Bell et al., 2005
; McGurk et al., 2005
). We are currently conducting studies to investigate the relationship of the improved cognitive skills evident in the current study to proxy and actual measures of community function. Third, the design of the study would have been improved by an independent measurement of the level of “cognitive challenge” produced by each intervention. While we assume that the processing of novel verbal information and the periodic content exams characteristic of the computer-training control would produce non-specific cognitive challenge that would be similar to that of drill-and-practice cognitive exercises, it remains unclear whether patients may have perceived one condition as more difficult than another. Fourth, the current remediation intervention selected for this study employed a “bottom-up” approach in which training was hierarchically organized such that elementary neurocognitive functions (e.g., simple sustained attention) were trained before more complex functions (e.g., verbal memory). It remains unclear to what degree our findings relate to “top-down” remediation approaches that emphasize training of multiple cognitive domains simultaneously, with procedures that are selected for their ability to promote task engagement (e.g., Medalia et al., 2001
). Future studies will be aimed at understanding what demographic, neurocognitive or symptom characteristics predict treatment responses to cognitive remediation interventions, how training-related improvements in neurocognition may be enhanced through pharmacologic manipulation, and the durability of observed specific and non-specific treatment effects after termination of these interventions.